Psychiatric Diagnoses Are Associated With Postoperative Disparities in Patients Undergoing Major Colorectal Operations.

BACKGROUND: Over 50% of hospitalized patients have comorbid psychiatric diagnoses, resulting in increased risk of morbidity such as longer lengths of stay, worse health-related quality of life, and increased mortality. However, data regarding colorectal surgery postoperative outcomes in patients with psychiatric diagnoses (PD) are limited. METHODS: We queried a single institution's National Surgical Quality Improvement Program from 2013-2019 for major colorectal procedures. Postsurgical outcomes for patients with and without PD were compared. Primary outcomes were prolonged length of stay (pLOS) and 30-day readmission. RESULTS: From a total of 1447 patients, 402 (27.8%) had PD. PD had more smokers (20.9% vs 15%) and higher mean body mass index (29.1 kg/m2 vs 28.2 kg/m2). Bivariate outcomes showed more surgical site infections (SSI) (10.2% vs 6.12%), reoperation (9.45% vs 6.35%), and pLOS (34.8% vs 29.0%) (all P values <.05) in the PD group. On multivariate analysis, PD had higher likelihood of reoperation (OR 1.53, 95% CI: [1.02-2.80]) and SSI (OR 1.82, 95% CI: [1.25-2.66]). DISCUSSION: Psychiatric diagnoses are a risk factor for adverse outcomes after colorectal procedures. Further studies are needed to evaluate the benefit of perioperative mental health support services for these patients.

Use of a 5-Item Modified Frailty Index for Assessing Outcomes After Hartmann's Reversal: An ACS-NSQIP Study.

BACKGROUND: Half of all patients with an end colostomy after sigmoid colectomy (Hartmann's procedure) never undergo Hartmann's reversal, frequently secondary to frailty. This retrospective cohort study evaluates the utility of a five-item modified frailty index (mFI-5) in predicting post-operative outcomes after Hartmann's reversal. METHODS: The National Surgery Quality Improvement Program (NSQIP) database captured patients with elective Hartmann's reversals from 2011 to 2020. Clinical covariates were evaluated with univariate analysis and modified Poisson regression to determine association with overall morbidity, overall mortality, and extended length of stay (eLOS) when categorized by mFI-5 score. RESULTS: 15,172 patients underwent elective Hartmann's reversal (91.6% open and 8.4% laparoscopic). Patients were grouped by mFI-5 score (0: 48.7%, 1: 38.2%, ≥ 2: 13.1%). Adjusted multivariable analysis showed frail patients (mFI-5≥2) had increased overall mortality (OR 2.23, 95% CI 1.21-4.11), morbidity (OR 1.23, 95% CI 1.12-1.35), and eLOS (OR 1.12, 95% 1.02-1.23). Among frail patients, a laparoscopic approach was associated with decreased overall morbidity (OR .64, 95% CI 0.56-.73) and decreased eLOS (OR .46, 95% CI 0.39-.54) when compared to open approach. DISCUSSION: An mFI-5 of ≥2 was associated with greater morbidity, mortality, and eLOS following Hartmann's reversal. However, there were no mortality or eLOS differences in patients with an mFI-5 of 1 and only a 14% increase in any morbidity, making these patients potentially good candidates for Hartmann's reversal. Furthermore, laparoscopic surgery was associated with a protective effect for overall morbidity and eLOS, potentially mitigating some of the risk associated with higher frailty scores.

Impact of Preoperative Factors in Patients With IBD on Postoperative Length of Stay: A National Surgical Quality Improvement Program-Inflammatory Bowel Disease Collaborative Analysis.

BACKGROUND: Patients with IBD are challenging to manage perioperatively because of disease complexity and multiple comorbidities. OBJECTIVE: To identify whether preoperative factors and operation type were associated with extended postoperative length of stay after IBD-related surgery, defined by 75th percentile or greater (n = 926; 30.8%). DESIGN: This was a cross-sectional study based on a retrospective multicenter database. SETTING: The National Surgery Quality Improvement Program-Inflammatory Bowel Disease Collaborative captured data from 15 high-volume sites. PATIENTS: A total of 3008 patients with IBD (1710 with Crohn's disease and 1291 with ulcerative colitis) with a median postoperative length of stay of 4 days (interquartile range, 3-7) from March 2017 to February 2020. MAIN OUTCOME MEASURES: The primary outcome was extended postoperative length of stay. RESULTS: On multivariable logistic regression, increased odds of extended postoperative length of stay were associated with multiple demographic and clinical factors (model p < 0.001, area under receiver operating characteristic curve = 0.85). Clinically significant contributors that increased postoperative length of stay were rectal surgery (vs colon; OR, 2.13; 95% CI, 1.52-2.98), new ileostomy (vs no ileostomy; OR, 1.50; 95% CI, 1.15-1.97), preoperative hospitalization (OR, 13.45; 95% CI, 10.15-17.84), non-home discharge (OR, 4.78; 95% CI, 2.27-10.08), hypoalbuminemia (OR, 1.66; 95% CI, 1.27-2.18), and bleeding disorder (OR, 2.42; 95% CI, 1.22-4.82). LIMITATIONS: Retrospective review of only high-volume centers. CONCLUSIONS: Patients with IBD who were preoperatively hospitalized, who had non-home discharge, and who underwent rectal surgery had the highest odds of extended postoperative length of stay. Associated patient characteristics included bleeding disorder, hypoalbuminemia, and ASA classes 3 to 5. Chronic corticosteroid, immunologic, small molecule, and biologic agent use were insignificant on multivariable analysis. See Video Abstract. IMPACTO DE LOS FACTORES PREOPERATORIOS EN PACIENTES CON ENFERMEDAD INFLAMATORIA INTESTINAL EN LA DURACIN DE LA ESTANCIA POSTOPERATORIA UN ANLISIS COLABORATIVO DEL PROGRAMA NACIONAL DE MEJORA DE LA CALIDAD QUIRRGICAENFERMEDAD INFLAMATORIA INTESTINAL: ANTECEDENTES:Los pacientes con enfermedad inflamatoria intestinal son difíciles de manejar perioperatoriamente debido a la complejidad de la enfermedad y a múltiples comorbilidades.OBJETIVO:Este estudio tuvo como objetivo identificar si los factores preoperatorios y el tipo de operación se asociaron con una estadía postoperatoria prolongada después de una cirugía relacionada con enfermedad inflamatoria intestinal, definida por el percentil 75 o mayor (n = 926, 30.8%).DISEÑO:Este fue un estudio transversal basado en una base de datos multicéntrica retrospectiva.ESCENARIO:Datos capturados de quince sitios de alto volumen en El Programa Nacional de Mejoramiento de la Calidad de la Cirugía-Enfermedad Intestinal Inflamatoria en colaboración.PACIENTES:Un total de 3,008 pacientes con enfermedad inflamatoria intestinal (1,710 con enfermedad de Crohn y 1,291 con colitis ulcerosa) con una mediana de estancia postoperatoria de 4 días (RIC 3-7) desde marzo de 2017 hasta febrero de 2020.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la extensión de la estancia postoperatoria.RESULTADOS:En la regresión logística multivariable, el aumento de las probabilidades de prolongar la estancia postoperatoria se asoció con múltiples factores demográficos y clínicos (modelo p<0.001, área bajo la curva ROC - 0.85). Los contribuyentes clínicamente significativos que aumentaron la duración de la estancia postoperatoria fueron la cirugía rectal (frente al colon) (OR 2.13, IC del 95 %: 1.52 a 2.98), una nueva ileostomía (frente a ninguna ileostomía) (OR 1.50, IC del 95 %: 1.15 a 1.97), hospitalización preoperatoria (OR 13.45, IC 95% 10.15-17.84), alta no domiciliaria (OR 4.78, IC 95% 2.27-10.08), hipoalbuminemia (OR 1.66, IC 95% 1.27-2.18) y trastorno hemorrágico (OR 2.42, IC 95% 1.22-4.82).LIMITACIONES:Revisión retrospectiva de solo centros de alto volumen.CONCLUSIONES:Los pacientes con enfermedad inflamatoria intestinal que fueron hospitalizados antes de la operación, que tuvieron alta no domiciliaria y que se sometieron a cirugía rectal tuvieron las mayores probabilidades de prolongar la estancia postoperatoria. Las características asociadas de los pacientes incluyeron trastorno hemorrágico, hipoalbuminemia y clases ASA 3-5. El uso crónico de corticosteroides, inmunológicos, agentes de moléculas pequeñas y de agentes biológicos no fue significativo en el análisis multivariable. (Traducción-Dr. Jorge Silva Velazco ).

Detection of Ischemic Colitis on Routine Lower Endoscopy and Its Implications After Repair of Ruptured Abdominal Aortic Aneurysm.

BACKGROUND: Ischemic colitis (IC) is a known significant complication after repair of a ruptured abdominal aortic aneurysm (rAAA). Lower endoscopy (colonoscopy or flexible sigmoidoscopy) is a helpful adjunct to aid decision making for surgical exploration. We believe routine use of lower endoscopy after rAAA repair provides better patient care through expeditious diagnosis and surgical care. METHODS: We performed a retrospective chart review of rAAA repairs from 2008 to 2019. All patients undergo screening lower endoscopy after rAAA repair at our institution. The incidence of IC, mortality, and diagnostic characteristics of routine lower endoscopy was analyzed. RESULTS: Of these, 182 patients underwent rAAA repair, among which 139 (76%) underwent routine lower endoscopy. Ischemic colitis of any grade was diagnosed in 25% of patients. The 30-day mortality was 11% compared to 19% in those without lower endoscopy. The presence of IC portended a 4-fold increase in mortality rate compared to those without (26% vs 6%, P = .005). Surgical exploration rate was 8% after routine lower endoscopy. Grade III ischemia on lower endoscopy had a sensitivity of 50% (95% CI 12-88) and specificity of 99% (95% CI 94-100) for transmural necrosis. DISCUSSION: We found increased incidence of IC and reliable diagnostic characteristics of routine lower endoscopy in predicting the presence of transmural colonic ischemia. There was decreased mortality with use of routine lower endoscopy but this was not statistically significant.

The Effect of an Enhanced Recovery Program on Elective Right Hemicolectomies for Crohn's Disease vs. Colon Cancer: A Retrospective Cohort Analysis.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are widely employed in colorectal surgery, successful in reducing postoperative morbidities and hospital length of stay (LOS). However, ERAS effects on the inflammatory bowel disease population remain unclear. This study examines the postoperative course of both Crohn's disease (CD) and colon cancer (CC) patients after elective right hemicolectomies and compares the effectiveness of ERAS protocol. METHODS: A retrospective analysis was performed on patients with CD and CC undergoing elective right hemicolectomies and ileocecectomies from January 2014 through June 2016 (pre-ERAS) and January 2017 through April 2019 (post-ERAS) from a single tertiary care center. Patient demographics and perioperative variables were examined, including prolonged postoperative ileus (PPOI), hospital LOS, and 30-day readmission. RESULTS: 98 CC patients and 91 CD patients met the inclusion criteria. The pre-ERAS CC and post-ERAS CC cohorts were significantly different: post-ERAS had fewer patients with congestive heart failure and chronic obstructive pulmonary disease and had higher albumin levels. The pre-ERAS CC cohort had significantly longer operative durations and higher rates of concomitant procedures than the post-ERAS CC cohort. Both patients with CC and CD had a reduction in LOS with implementation of ERAS, decreasing by 2.24 days (P = .002) and 1.21 days (P = .038), respectively. There was a reduction in rates of organ space infections with CD (pre .132, post .00, P = .007). There was a trend towards an increased rate of PPOI with CD (Pre .079, Post .226, P = .062). DISCUSSION: The ERAS protocol significantly reduced LOS for both groups, without increasing 30-day readmission rates or other morbidities.

The Impact of an Enhanced Recovery Program on Loop Ileostomy Closure.

BACKGROUND: The implementation of enhanced recovery after surgery (ERAS) protocols has decreased the length of stay (LOS) and complications in colorectal procedures. However, little data has been published on the subset of patients undergoing loop ileostomy closure. We investigated the outcomes of loop ileostomy reversals prior to and after initiation of an ERAS protocol. METHODS: Patients undergoing ileostomy reversal over a 5-year period by 4 colorectal surgeons were studied and divided into pre-ERAS patients and ERAS patients in a retrospective, case-control study. Patient demographics, comorbidities, LOS, underlying disease process, index intra-abdominal procedure, readmission rate, and complications were evaluated. RESULTS: Overall, 208 patients were analyzed 149 pre-ERAS and 59 ERAS-with median LOS significantly lower in the ERAS group than the pre-ERAS group (50.8 hours vs. 96.1 hours, P < .0001). In subgroup analysis, the LOS was significantly lower if the index procedure performed was laparoscopic when comparing ERAS to pre-ERAS (49.9 hours vs. 96.6 hours, P < .001). ERAS did not confer a significant decrease in the LOS during ileostomy reversal with open index procedures (72.9 hours vs. 95.5 hours, P = .05). CONCLUSION: Utilizing an ERAS protocol is safe and effective for loop ileostomy closure with a shorter LOS and no difference in complication rates or 30-day readmission rates.

After Elective Sigmoid Colectomy for Diverticulitis, Does Recurrence-Free Mean Symptom-Free?

After elective sigmoidectomy for diverticulitis, patients may experience persistent abdominal symptoms. This study aimed to determine the incidence and characteristics of persistent symptoms (PSs) and their risk factors in patients who had no reported recurrence after elective sigmoidectomy. Patients who underwent elective sigmoidectomy for diverticulitis from 2002 to 2016 at a tertiary academic colorectal surgery practice were included. After retrospective review of medical records, patients were contacted with a questionnaire to inquire about recurrence of diverticulitis and persistent abdominal symptoms since resection. Outcomes examined were prevalence of and risk factors for PSs after elective sigmoidectomy. Of 662 included patients, 346 completed the questionnaire and had no recurrent diverticulitis. PSs were reported by 43.9 per cent of the patients. The mean follow-up was 87 months. Female gender and preoperative diagnosis of irritable bowel syndrome were independent risk factors for PSs (Relative Risk 1.65, P < 0.001 and Relative Risk 1.41, P = 0.014). Previous IV antibiotics treatment was associated with PSs (P = 0.034) but not with a significant risk factor. As the follow-up interval increased, prevalence of PSs decreased (P = 0.006). More than 40 per cent of patients experienced persistent abdominal symptoms after sigmoidectomy for diverticulitis. Female patients and those with irritable bowel syndrome were at significantly increased risk.

Elective Laparoscopic Sigmoid Colectomy for Diverticulitis-an Updated Look at Recurrence After Surgery.

BACKGROUND: Surgical management of diverticulitis is evolving and the decision to offer elective sigmoidectomy for diverticulitis has become more individualized. However, preoperative variables that may predict recurrent diverticulitis after resection and guide surgical decision-making were not well studied. METHODS: This was a retrospective chart review with a prospective questionnaire follow-up of patients. Patients who underwent elective sigmoidectomy for diverticulitis from 2002 to 2016 at a tertiary academic colorectal surgery practice were included and their medical records reviewed. They were then contacted with a questionnaire to inquire about recurrence of diverticulitis since resection. The primary outcome was rate of recurrent diverticulitis after elective sigmoidectomy. The secondary outcome was risk factors for recurrence after sigmoidectomy. RESULTS: Of 662 patients who underwent elective sigmoidectomy for diverticulitis, 361 had long-term follow-up data available. Mean follow-up was 86 months. Indication for surgery was uncomplicated recurrent diverticulitis in 50%. Recurrent diverticulitis developed in 15 (4.2%) patients. Mean time to recurrence was 55 (range, 6-109) months. All recurrences were confirmed by CT scan. Univariate analysis showed that preoperative diagnosis of irritable bowel syndrome and uncomplicated recurrent diverticulitis was significantly more prevalent in patients who experienced recurrent diverticulitis after sigmoidectomy (p = 0.049 and p = 0.02); however, these variables did not predict recurrence after resection. CONCLUSIONS: Overall rate of recurrent diverticulitis after elective sigmoidectomy was 4.2%. Preoperative diagnosis of irritable bowel syndrome and uncomplicated recurrent diverticulitis was associated with but not significant predictor of recurrence after elective resection.

Laparoscopic Surgery for Diverticular Fistulas: Outcomes of 111 Consecutive Cases at a Single Institution.

BACKGROUND: The purpose of this study was to review our experience with laparoscopic colectomy and fistula resection, evaluate the frequency of conversion to open, and to compare the perioperative courses of the complete laparoscopic and conversion groups. METHODS: This study is a retrospective analysis of 111 consecutive adult patients with diverticular fistulae diagnosed clinically or radiographically over 11 years at a single institution. Five patients were excluded for preoperative comorbidities. The remaining 106 consecutive patients underwent minimally invasive sigmoid colectomy with primary anastomosis. Preoperative, intraoperative, and postoperative variables were collected from the colorectal surgery service database. A retrospective cohort analysis was performed between laparoscopic and converted groups. RESULTS: Within the group, 47% had colovesical fistulas, followed by colovaginal, coloenteric, colocutaneous, and colocolonic fistulas. The overall conversion rate to laparotomy was 34.7% (n = 37). The most common reason for conversion was dense fibrosis. Mean operative time was similar between groups. Combined postoperative complications occurred in 26.4% of patients (21.4% laparoscopic and 37.8% converted, p = 0.075). Length of stay was significantly shorter in the laparoscopic group (5.8 vs 8.1 days, p = 0.014). There were two anastomotic leaks, both in the open group. There were no 30-day mortalities. CONCLUSIONS: Laparoscopic sigmoid colectomy for diverticular fistula is safe, with complication rates comparable to open sigmoid resection. We identify a conversion rate which allows the majority of patients to benefit from minimally invasive procedures.

Impact of Interhospital Transfer on Outcomes in Non-emergency Colorectal Surgery.

BACKGROUND: A paucity of data exists on the impact of transfer status on outcomes for patients undergoing non-emergency (urgent) colorectal surgery. This study characterized transferred patients undergoing urgent colorectal surgery and determined which patient comorbidities significantly contributed to poor outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2013 was used. Urgent direct admissions undergoing colon, rectum, or small bowel operations were compared to urgent transfers using bivariate and multivariable analysis models. Primary outcomes were overall complications, hospital length of stay, and mortality. RESULTS: A total of 82,151 admissions were analyzed. After multivariable analysis, direct admission patients had nearly similar risk of complications (RR = 0.95; 95% CI 0.91-0.99) and length of hospital stay (7% shorter; 95% CI 4-9%), as well as no difference in mortality (RR = 0.94; 95% CI 0.80-1.11). CONCLUSIONS: Transfer status alone confers minimal risk toward higher complication rates and longer hospital length of stay in patients undergoing urgent colorectal surgery, and the poor outcomes observed in this cohort are largely due to patient comorbidities and disease severity. Our results suggest that outcomes in transferred colorectal surgery patients undergoing urgent operations depend mainly on operative acuity and clinical factors, and to a lesser degree transfer status.

Complications and surgical outcomes after interhospital transfer vs direct admission in colorectal surgery: A National Surgical Quality Improvement Program analysis.

BACKGROUND: Interhospital transfer is common among patients undergoing colorectal surgery. The purpose of this study was to determine surgical outcomes after transfer vs direct admission in patients undergoing colorectal surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database from 2010 to 2012 was used. Colorectal operations were selected, including both emergency and nonemergency cases. Transfers were compared with direct admissions using a complex comorbidity analysis model. Primary outcomes of interest were mortality, extended hospital length of stay, and complication rates. RESULTS: The study included 121,040 admissions. After adjusting for multiple patient factors and comorbidities, nonemergency transfers still had higher mortality rates (RR = 1.20; P < .05), longer length of hospital stay (RR = 1.24; P < .05), and higher complication rates (RR = 1.18; P < .05). CONCLUSIONS: Preoperative hospital transfer is common among patients requiring colorectal surgery. Despite extensive propensity score matching, nonemergency transfers have higher rates of mortality, longer length of hospital stay, and higher overall complication rates compared with direct admissions. Transfer status is an important variable in hospital performance models and should be taken into consideration when analyzing hospital outcomes.

Incidence of Ostomy Site Incisional Hernias after Stoma Closure.

This study sought to evaluate the incidence of ostomy site incisional hernias after stoma reversal at a single institution. This is a retrospective analysis from 2001 to 2011 evaluating the following demographics: age, gender, indication for stoma, urgent versus elective operation, time to closure, total follow-up time, the incidence of and reoperation for stoma incisional hernia, diabetes, postoperative wound infection, smoking status within six months of surgery, body mass index, and any immunosuppressive medications. A total of 365 patients were evaluated. The median follow-up time was 30 months. The clinical hernia rate was 19 percent. Significant risk factors for hernia development were age, diabetes, end colostomies, loop colostomies, body mass index >30, and undergoing an urgent operation. The median time to clinical hernia detection was 32 months. Sixty-four percent of patients required surgical repair of their stoma incisional hernia. A significant number of patients undergoing stoma closure developed an incisional hernia at the prior stoma site with the majority requiring definitive repair. These hernias are a late complication after stoma closure and likely why they are under-reported in the literature.

Combination propofol/ketamine is a safe and efficient anesthetic approach to anorectal surgery.

PURPOSE: Concerns persist regarding respiratory complications from combination deep intravenous sedation and local anesthesia for prone position anorectal surgery. We examined the safety and efficacy of this approach by using a propofol-based and ketamine-based technique. METHODS: A retrospective review was conducted on all patients undergoing anorectal surgery. Outcomes (perioperative times, specific complications) were compared with respect to operative position and anesthetic approach. Significance was determined using Student's t-test and chi-squared analysis. RESULTS: Surgery was performed on 448 patients during a three-year period. There was no significant difference in the two anesthetic groups with regard to age and gender. There were 19 anesthesia-related adverse events occurring in the study group (Monitored Anesthesia Care Group): nausea and vomiting (n = 8), airway obstruction necessitating conversion to general anesthesia (n = 2), excessive pain (n = 2), urinary retention (n = 5), and hospital readmission (n = 2). These occurred in <5 percent of those receiving the combination technique (19/407). Although there was no difference in total procedural time, there was a significant difference in total time spent in the operating room (P = 0.001) and in the hospital overall (P = 0.002). Of the patients receiving combination technique anesthesia, only 31 (7 percent) required the use of the postanesthesia care unit. All patients receiving general anesthesia (n = 23) required the postanesthesia care unit. CONCLUSIONS: Combination deep intravenous sedation with local anesthesia based on propofol and ketamine is a safe and effective technique for prone-position anorectal surgery. It results in decreased use of the postanesthesia care unit and earlier hospital discharge, reflecting a more efficient use of hospital resources.

Caspase-3 drives apoptosis in pancreatic cancer cells after treatment with gemcitabine.

Pancreatic cancer remains a highly chemoresistant malignancy. Gemcitabine, the most effective first-line agent available, acts by disrupting cellular replication. Caspases belong to a family of proteases that function as key components of the apoptotic death machinery. We investigated the mechanisms by which gemcitabine blocks proliferation and whether it can induce apoptosis in pancreatic cancer cells. Quiescent pancreatic cancer cells (BxPC-3) were stimulated to proliferate (10% fetal calf serum) with or without gemcitabine, PS-341 (26S proteasome inhibitor), or both. Proliferation was measured by MTT assay and apoptosis by propidium iodine staining. To determine activation of the apoptotic regulatory cell proteins, caspase-3 and cleavage of poly(ADP-ribose)polymerase (PARP) into its 85-kDa fragment were assessed by Western blotting. Gemcitabine at even low doses (10 micromol/L) significantly inhibited cellular proliferation, whereas PS-341 (10 nmol/L) had no effect. With combined treatment, PS-341 potentiated the antiproliferative effects of gemcitabine (P=0.001). At 48 hours, the apoptotic fraction was greatly enhanced by the presence of PS-341 compared with gemcitabine alone. Caspase-3 accumulated as early as 30 minutes and was associated with cleavage of PARP to its apoptotic fragment. Gemcitabine, a nucleoside analogue, may in part exert its antiproliferative effects by directing pancreatic cancer cells to a default pathway of apoptosis. 26S proteasome inhibition potentiates this effect, suggesting its potential clinical value against chemoresistance in pancreatic cancer.

Increased expression of NF-kappa B subunits in human pancreatic cancer cells.

BACKGROUND: Activation of NF-kappa B-dependent antiapoptotic genes may factor in the chemoresistance of pancreatic cancer. It is not known whether NF-kappa B subunit composition changes during oncogenesis and regulates overall NF-kappa B activation. We compared the relative expression of NF-kappa B subunits with nuclear activation of p65 between variably differentiated pancreatic cancer cells. MATERIALS AND METHODS: Proliferating human pancreatic cancer cells (PANC-1, BxPC-3) and nonmalignant intestinal cells (FHS 74 Int) were harvested. Baseline expression of NF-kappa B subunits (p65, p52, p50, c-Rel) and its inhibitor I kappa B-alpha were determined by Western blot. Nuclear NF-kappa B p65 activity was measured by ELISA. Results were analyzed by ANOVA (P < 0.05) and Tukey's HSD for pairwise comparisons when appropriate (P < 0.05). RESULTS: Constitutive expression of NF-kappa B subunits was detected in proliferating, intestinal cells (FHS 74 Int). Both cytoplasmic (I kappa B-alpha, p50, p52, p65) and nuclear (p50, p52, p65, c-Rel) NF-kappa B subunits were significantly increased in both PANC-1 and BxPC-3 cells compared to FHS 74 Int. While nuclear p65 subunit levels were similarly elevated, actual p65 activity was only significantly greater in PANC-1 cells compared to either BxPC-3 or FHS 74 Int (P < 0.05). CONCLUSIONS: Compared to nonmalignant proliferating intestinal cells, these pancreatic cancer cell lines have increased levels of NF-kappa B subunits. Actual nuclear NF-kappa B activity, however, appears to correlate more with degree of tumor differentiation than with NF-kappa B subunit expression.

Preoperative chemoradiation in resectable pancreatic cancer.

Despite advancements in the field of surgical oncology, the diagnosis of pancreatic cancer still carries a grave and dismal prognosis. Surgery alone for adenocarcinoma of the pancreatic head or uncinate process has a median survival time of 12 months. These grim statistics have led many to study the effects of combined multimodality therapy in the fight against pancreatic cancer. The long recovery time associated with pancreaticoduodenectomy has resulted in as many as 25% of patients unable to proceed with planned adjuvant therapy. For these reasons preoperative or neoadjuvantc hemoradiation therapy (CRT) has been evaluated. Pre-operative CRT ensures that all eligible patients receive the benefits of multimodality therapy, and patients who manifest metastatic disease on restaging evaluations are spared the morbidity of an unnecessary laparotomy. Multimodality therapy appears to lengthen the survival duration in patients with pancreatic cancer. It also affords a selection advantage, in that patients with aggressive disease biology with advanced metastatic disease following CRT are spared the morbidity of surgery. Conversely, a limited subset of patients may even be downstaged, allowing for a potentially curative resection. In this article we review the current status of neoadjuvant chemoradiation in adenocarcinoma of the pancreas. We discuss its rationale in light of the reported strengths and weaknesses of postoperative adjuvant CRT.